A retrospective study of hydrocortisone continuous rate infusion compared with administration of dexamethasone boluses in dogs with adrenal crisis

Abstract

Background

Evidence indicating the optimal treatment protocol for dogs in adrenal crisis is lacking.

Objectives

Compare outcomes of dogs presented in adrenal crisis treated with either hydrocortisone (HC) continuous rate infusion (CRI) or intermittent dexamethasone (DEX) administration.

Animals

Thirty‐nine client‐owned dogs.

Methods

Multi‐institutional retrospective observational study (July 2016‐May 2022) including dogs diagnosed with adrenal crisis and with available sequential blood work during hospitalization. Dogs were excluded if already on treatment with exogenous corticosteroids. Outcomes assessed included duration of hospitalization, survival, number of repeat measurements of electrolyte concentrations, and time to normalization of electrolyte and acid‐base status.

Results

No significant difference was found between the groups for hospitalization time (P = .41; HC median [range] 48 h [19‐105 h]; DEX 57 h [17‐167 h]) nor case fatality rate 2/28 in the DEX group and 0/11 in the HC group (P = 1), nor in number of measurements of electrolyte concentrations (P = .90; HC 4 [2‐10]; DEX 4.5 [2‐15]). No significant differences were found between the 2 treatment groups in time to normalization of serum Na (P = .30; HC 33 h [7‐66 h]; DEX 16 h [1.5‐48 h]), K (P = .92; HC 17 h [4‐48 h]; DEX 16 h [1.25‐60 h]) or Na/K ratio (P = .08; HC 17 h [8‐48 h]; DEX 26 h [1.5‐60 h]).

Conclusions

This study detected no difference in outcomes for dogs in adrenal crisis treated with either DEX boluses or HC CRIs.

Abbreviations

ACTH

adrenocorticotropic hormone

APPLE_fast

Acute Patient Physiological and Laboratory Evaluation fast

CRI

constant rate infusion

DEX

dexamethasone

HC

hydrocortisone

HPA

hypothalamic‐pituitary‐adrenal

LRS

Lactate Ringer's Solution

1. INTRODUCTION

Hypoadrenocorticism (Addison's disease) is an uncommon endocrine condition characterized by glucocorticoid deficiency, mineralocorticoid deficiency or both. The incidence in dogs varies between 0.3% and 1.1%, with approximately 30% of affected dogs first examined because of adrenal crisis. ¹ , ²

Primary hypoadrenocorticism is the most common form of hypoadrenocorticism in dogs. An adrenal crisis is an endocrine emergency needing immediate medical intervention. ³ Although there is currently a wealth of information regarding the pathogenesis, clinical presentation, diagnosis, and long‐term treatment of hypoadrenocorticism in dogs, there is still a paucity of evidence investigating the optimal therapy for dogs presenting with acute adrenal crises. ¹ , ⁴ , ⁵ , ⁶ , ⁷

These emergency cases have usually been treated with aggressive volume resuscitation combined with the administration of rapidly acting glucocorticoids. In veterinary medicine, DEX or prednisolone are the most frequently administered exogenous glucocorticoids. ⁷ However, human medicine guidelines indicate HC to be the first choice in patients presenting with adrenal crisis. ⁸

Reported advantages of using HC over DEX and prednisolone are the balanced glucocorticoid and mineralocorticoid activity and its short half‐life, which means that if erroneously administrated to a patient without hypoadrenocorticism it is unlikely to have relevant long‐term consequences. Hydrocortisone is relatively inexpensive, has a long shelf‐life, and is widely available. ⁸

Dexamethasone is often used in veterinary medicine, where timely adrenocorticotropic hormone (ACTH) stimulation test results are often lacking, because of its lack of direct interference with the cortisol assay, although it will still result in depression of the hypothalamic‐pituitary‐adrenal (HPA) axis.

The use of HC continuous rate infusion (CRI) in 30 dogs in adrenal crisis treated with administration of intravenous fluid therapy and a 0.5 to 0.625 mg/kg/h HC CRI was a safe and effective protocol leading to a rapid resolution of electrolyte abnormalities with a median hospitalization time of 2 days. ⁹

Of dogs with hypoadrenocorticism presenting in crisis treated either with an HC CRI or DEX/prednisolone no benefits in the HC CRI group in terms of time to electrolyte normalization and hospitalization times were longer in the HC CRI group were detected. ¹⁰

The current study investigated outcomes of dogs diagnosed with adrenal crisis treated with either HC CRI or DEX intravenous boluses at 3 UK‐based referral institutions over a 6‐year period. The study's objectives were to establish and compare the effects of DEX boluses and HC CRI in dogs presented with adrenal crisis. Specifically, the primary outcome considered was the time to normalization of electrolytes and acid‐base status, while secondary outcomes included total hospitalization time, electrolyte recheck frequency, and rate of survival to discharge. The authors hypothesized that HC CRI would correct metabolic and electrolyte imbalances more promptly than DEX boluses, allowing a shorter hospitalization time.

2. MATERIALS AND METHODS

Electronic medical records were retrospectively searched from March 2016 to May 2022 for dogs diagnosed with adrenal crisis. Dogs were included if they displayed clinical signs and electrolyte abnormalities indicative of typical hypoadrenocorticism. These included at least 1 of hyponatremia, hyperkalemia, or a Na/K ratio <27, with concurrent signs of gastrointestinal disease and evidence of hypoperfusion. Clinical suspicion had to be followed by a consistent ACTH stimulation test performed before exogenous corticosteroid administration. Dogs also had to have sequential venous blood gas analysis (every 6‐12 h) performed during hospitalization, and for these results to be available. Dogs were excluded if they had been treated with exogenous corticosteroids within 48 h of presentation or if already on long‐term corticosteroid treatment for previously diagnosed hypoadrenocorticism.

Data collected included signalment (age, sex, reproductive status, and breed), physical exam findings, time of admission and discharge, packed cell volume, total solids, hematology, serum albumin, and creatinine concentrations at the time of admission, pre‐ and post‐ACTH stimulation test serum cortisol concentrations, and serial venous blood gas analysis (including electrolytes, blood glucose, and lactate) throughout hospitalization. Venous blood gas analysis data were measured through either a benchtop analyzer (ABL800 FLEX blood gas analyzer, Radiometer Ltd, Crawley, UK) or a handheld one (epoc Veterinary Blood Gas Electrolyte and Critical Care Analyzer, Woodley Equipment Company Ltd, Bolton, UK). Analyzers were used consistently at all time points for individual dogs. Reference ranges for the investigated values were consistent between the 2 analyzers used in this study, eliminating the potential for incongruences when interpreting interpatient results.

Hematology and serum biochemistry data were also obtained from in‐house benchtop analyzers (Idexx Procyte hematology analyzer, Idexx, Wetherby, UK; Siemens Advia 2120, Siemens Healthcare Limited, Camberley, UK; Beckman Coulter AU480, Beckman Coulter Inc., High Wycombe, UK; Idexx VetStat Electrolyte and blood gas analyzer, Idexx, Wetherby, UK; Idexx Catalyst DX Blood Chemistry Analyzer, Idexx, Wetherby, UK). Pre‐ and post‐ACTH stimulation test serum cortisol concentrations were obtained either via external laboratories (Dick White Referral Laboratory, Six Mile Bottom, UK; VPG Laboratory, Leeds, UK; Idexx Laboratories, Wetherby, UK) or in‐house analyzers (Woodley VCheck V200, Woodley Equipment Company Ltd, Bolton, UK; Immulite 1000 Analyzer, Siemens Healthcare Limited, Camberley, UK). Survival to discharge was also recorded and for statistical analysis, dogs were grouped into either DEX or HC groups.

If sodium or potassium were normal upon admission or did not normalize until discharge, these dogs were omitted from the comparison of the time until normalization of sodium or potassium.

2.1. Statistical methods

Data were organized in Microsoft Excel (Microsoft, USA); data analyses were performed in R (R version 4.2.2) using RStudio (version 2023.03.0 + 386). Data were assessed for normality by visual assessment of histograms and q‐q plots. Data are presented as mean (±SD) or median (range). Normally distributed variables were compared using Student's t‐test and nonnormally distributed data were compared using the Mann‐Whitney‐U test. Categorical data were compared using Fisher's exact test. Changes over time were assessed using a repeated measures model with the variable of interest as the dependent variable and treatment group and time as independent variables. Statistical significance was set at P < .05.

3. RESULTS

A total of 39 dogs met the inclusion criteria and were reviewed. The mean age of the study sample was 5.97 years (± 3.78 years). The median weight was 16 kg (range, 3.3‐37 kg).

The study cohort was composed of 18 females, 2 entire and 16 neutered, and 21 males, 4 entire and 17 neutered. A variety of breeds were represented in this study including 16 crossbreed dogs, of which 8 were poodle crosses, 4 Labrador retrievers, 3 cocker spaniels, 2 Boston terriers, 2 bearded collies, 2 Maltese dogs, and 1 each of pug, German shepherd dog, Border terrier, German pointer, boxer, West Highland white terrier, basset hound, springer spaniel, lurcher, and Chihuahua.

Hematology and serum biochemical values on admission are summarized in Table 1.

TABLE 1.

Summary of presenting hematologic values for all dogs.

Variable		Mean	SD	Median	Min	Max
Na (mEq/L)		134.57	10.38	134.90	98.00	155.40
K (mEq/L)		6.56	1.36	6.45	4.10	9.50
Na/K		21.8	5.82	20.85	13.6	37
Cl (mEq/L)		107.19	7.74	107.30	78.00	122.00
HCO3 (mEq/L)		15.89	3.41	15.25	8.30	27.80
pH		7.32	0.09	7.32	7.11	7.46
PCV (%)		0.49	0.12	0.49	0.22	0.80
TS (g/L)		64.02	12.20	64.00	40.00	88.00
Creatinine	(μmol/L)	217.79	149.88	183.00	59.00	786.0
	mg/dL	2.46	1.7	2.07	0.67	8.89
Leucocytes (109/L)		4.23	3.19	3.68	1.05	17.27
Eosinophils (109/L)		0.63	0.47	0.60	0.00	1.83
Neutrophils (109/L)		9.02	8.30	7.27	0.09	45.69
Albumin (g/L)		28.17	7.21	29.00	16.00	43.00

Eleven dogs were treated with HC CRI and 28 with intravenous administration of DEX. No significant differences between these groups were present for age (P = .33; HC 5.1 years [±3.7 years]; DEX 6.3 years [±3.8 years]), sex (P = .17; HC 3/11 females, 8/11 males; DEX 15/28 females, 13/18 males), neuter status (P = .32; HC 8/11 neutered, 3/11 entire; DEX 25/28 neutered, 3/28 entire), weight (P = .15; 13.4 kg [±8.1 kg]; DEX 17.8 kg [±8.9 kg]), Cl (P = .62; HC 107 mEq/L [78‐118 mEq/L]; DEX, 107 mEq/L [99‐122 mEq/L]), K (P = .66; HC 6.5 mEq/L [5.5‐8.0 mEq/L]; DEX 6.4 mEq/L [4.1‐9.5 mEq/L]), iCa (P = .96; HC 5.24 mg/dL [1.31 mmol/L] [4.68‐7.6 mg/dL] [1.17‐1.9 mmol/L]; DEX 5.24 mg/dL [1.31 mmol/L] [4.52‐9.28 mg/dL] [1.13‐2.32 mmol/L]), PCV (P = .17; HC 0.57 [0.33‐0.80]; DEX 0.48 [0.22‐0.65]), TS (P = .28; HC 67 g/L [54‐88 g/L]; DEX 62 g/L [40‐84 g/L]) or HCO₃ (P = .69; HC 16.3 mEq/L [8.3‐27.8 mEq/L]; DEX 15.2 mEq/L [13.2‐19.5 mEq/L]).

Serum pH (P = .005) was significantly lower in the HC group at admission. Specifically, pH values were available for 24/27 dogs in the DEX group and 11/11 dogs in the HC group. Median pH in the DEX group was 7.34 (range, 7.2‐7.46; IQR 7.28‐7.42), 8/24 dogs had a pH within normal limits (reference range, 7.36‐7.44), 2/24 had an initial alkalemia and 14/24 had an initial acidemia. In the HC group, all dogs had an initial acidemia (median 7.26; range, 7.11‐7.34; IQR 7.19‐7.29).

Serum Na values at admission were available for all dogs and were significantly lower in the HC group at admission (P = .05). The median serum Na value in the DEX group was 136.5 mEq/L (range, 98‐155 mEq/L; IQR 131.8‐141.3 mEq/L), 10/28 were within normal limits (reference range, 139‐154 mEq/L), 1/28 dog was hypernatremic and 17/28 were hyponatremic. In the HC group, the median serum Na value was 130 mEq/L (range, 120‐139 mEq/L; IQR 126.5‐134.6 mEq/L), 2/11 had a normal serum Na concentration and 9/11 were hyponatremic. Starting and final values for each dog are shown in Figure 1.

FIGURE 1.

Starting and final values for selected blood values. Dexamethasone‐treated cases are red, and hydrocortisone‐treated cases are blue. Green lines represent the upper and lower ranges of the reference interval for each parameter.

Median time to normalization of Na was 16 h in the DEX group (n = 12) (range, 1.5‐48 h) and 33 h in the HC group (n = 4) (range, 7‐66 h) with no significant difference identified (P = .3). The median time to normalization of K was 16 h in the DEX group (n = 18) (1.25‐60 h) and 17 h in the HC group (n = 10) (4‐48 h), again with no statistical difference identified (P = .92) (Figures 2 and 3). There was no significant difference in time to normalization of the Na/K ratio between groups with a median time of 26 h (range, 1.5‐60 h) in the DEX group (n = 17) and 17 h (range, 8‐48 h) in the HC group (n = 11) (P = .08) (Figure 4).

FIGURE 2.

Time to normalization of serum Na concentration in the DEX and HC groups.

FIGURE 3.

Time to normalization of serum K concentrations in the DEX and HC groups.

FIGURE 4.

Time to normalization of Na/K ratio in the DEX and HC groups.

Further analysis was performed by looking at the first and last measurements of serum concentrations of Na, K, Cl, HCO₃, iCa, and pH considered as categorical variables classified as low, normal, and high (Table 2). No significant differences were found between treatment groups for any of the proportions of dogs starting and ending in each group (low, normal, and high) nor dogs whose values normalized during hospitalization. However, 3/10 dogs in the DEX group that started with a normal serum Na were hypernatremic at the end of treatment.

TABLE 2.

Summary of serum electrolytes and acid‐base status (analyzed as categorical variables) of dogs in the DEX and HC groups at first and last blood analysis.

Variable	Presentation				Final
	Low	Normal	High	Missing	Low	Normal	High	Missing
Sodium‐DEX	17	10	1	0	6	18	4	0
Sodium‐HC	9	2	0	0	6	5	0	0
K‐DEX	0	7	21	0	1	24	3	0
K‐HC	0	1	10	0	0	11	0	0
Cl‐DEX	20	4	2	2	12	8	7	1
Cl‐HC	9	1	1	0	8	1	1	0
iCa‐DEX	2	9	6	11	2	9	2	15
iCa‐HC	1	7	2	1	1	9	0	1
HCO‐DEX	22	2	0	4	10	14	2	2
HCO‐HC	7	3	1	0	2	4	5	0
pH‐DEX	14	8	2	4	4	11	11	2
pH‐HC	11	0	0	0	1	8	2	0

Significant differences were found over time for all variables during the first 48 h of treatment, largely reflecting normalizing values, these are summarized in Figure 5. Significant differences were found in absolute values of serum Na (P = .01) and bicarbonate (P = .04) concentrations between the 2 treatment groups over the first 48 h of treatment. The rate of change between treatment groups was significant only for serum pH (P = .005).

FIGURE 5.

Developments for all variables over the first 48 hours of treatment split by treatment group. Dexamethasone‐treated cases are red, and hydrocortisone‐treated cases are blue. Gray lines represent the 95% CI for the variable in each treatment group at that time. Green lines represent the upper and lower ranges of the reference interval for each parameter.

The median number of electrolytes rechecks during hospitalization was 4 (range, 2‐15) with a median of 4 (2‐10) in the HC group and 4.5 (2‐15) in the DEX group with no significant difference (P = .90). No significant difference was found when the number of checks was divided by the hospitalization time (checks per hour) (P = .45).

Two dogs died, these were hospitalized for 10 days and 3 days, respectively. Both dogs presented with concurrent diseases, 1 had septic endocarditis with secondary immune‐mediated hemolytic anemia and the other had been diagnosed with diabetes mellitus. Both dogs were euthanized because of clinical deterioration and predicted poor prognosis. No significant difference was found in case fatality between the 2 treatment groups, 2/28 in the DEX group and 0/11 in the HC group (P = 1).

The surviving dogs had a median hospitalization time of 50 h with a range of 17 h to 167 h. There was no significant difference between the DEX and HC groups (P = .41) with HC dogs staying a median of 48 h (19‐105 h) and DEX dogs a median of 57 h (17‐167 h) (Figure 6).

FIGURE 6.

Hospitalization time for survivor dogs in the DEX and HC groups.

Information regarding the type of intravenous fluid received was available in all cases. Overall, 15/39 cases were administered 0.9% saline solution and 24/39 were administered Lactate Ringer's Solution (LRS). In the HC group, 5/11 were administered saline and 6/11 LRS. In the DEX group, 10/28 cases were administered saline, and 18/28 cases LRS. No significant difference was found in the rate of change for any of the serum electrolytes and pH values between dogs receiving 0.9% saline or LRS (Figure 7).

FIGURE 7.

Developments for all variables over the first 48 hours of treatment split by intravenous fluid therapy group. LRS‐treated cases are purple, and 0.9% NaCl‐treated cases are yellow. Gray lines represent the 95% CI for the variable in each treatment group at that time. Green lines represent the upper and lower ranges of the reference interval for each parameter.

Dose regimens for both drugs showed a wide variation within the study groups considered. Hydrocortisone was administered at a dose of 0.5 mg/kg/h in 7/11 dogs, 1/11 dog received a dose of 0.3 mg/kg/h, and in 3/11 dogs the dose was not specified. Dexamethasone dosing was variable in between cases, with a median of 0.15 mg/kg; 6/29 dogs received immunosuppressive doses (0.3‐1 mg/kg), 21/29 anti‐inflammatory doses (0.05‐0.1 mg/kg) and 2/29 physiological doses (0.03‐0.04 mg/kg).

Emergency treatment of hyperkalemia, either with calcium gluconate or glucose/insulin or a combination of the 2, was administered in 4/11 and 8/28 of dogs in the HC and DEX groups respectively. This was not found to be significantly different between treatment groups (P = .71).

4. DISCUSSION

The optimal treatment for adrenal crisis in dogs is currently unknown. The literature focuses on aggressive intravenous fluid therapy combined with a source of rapid‐acting glucocorticoids to achieve concurrent volume resuscitation and electrolyte correction. ⁵ The most commonly reported hormone replacement strategy for adrenal crisis in the United Kingdom is intravenous administration of DEX, followed by oral administration of prednisolone and fludrocortisone long‐term. ⁷ , ¹¹ , ¹² In human medicine, HC is the exogenous corticosteroid of choice rather than DEX. ⁸ The rationale for this is multifactorial, including that HC possesses equipotent mineralocorticoid and glucocorticoid activity, which makes it a theoretically ideal replacement. Hydrocortisone is widely available and relatively inexpensive, and because of its short half‐life, it is considered safe even if administered to patients with nonconfirmed hypoadrenocorticism. There is limited literature on the use of HC in dogs. Experimental studies in healthy dogs demonstrate doses of 0.5 to 0.625 mg/kg/h provide sufficient increases in circulating cortisol concentrations to potentially compensate for acute adrenal hypofunction. ¹³ A retrospective case series confirmed the safety and effectiveness of the clinical use of intravenous administration of HC in dogs presented with adrenal crisis. ⁹ Recently a retrospective study comparing HC CRI with the administration of DEX boluses or oral prednisolone confirmed the safety of HC administration in dogs presented with adrenal crisis. No additional benefits were demonstrated in dogs receiving HC compared to those receiving either DEX or prednisolone. Furthermore, the dogs in the HC group showed a significantly longer hospitalization time with more intensive monitoring performed. ¹⁰

The current study showed that both intravenous administration of DEX boluses and HC CRIs were safe and effective in correcting electrolyte and acid‐base abnormalities in dogs presented with acute adrenal crisis. No statistically significant difference was found in terms of time to normalization of serum sodium or potassium value or sodium to potassium ratio. Concerns have been raised regarding the rate of serum sodium correction with the use of HC; however, our findings did not show an unsafe rate of sodium correction. ⁹ Furthermore, the 3 dogs with a final serum sodium concentration above reference ranges were in the DEX group; possibly indicating that the mineralocorticoid effects of HC were protective.

Hyperkalemia is a major concern in dogs presenting with adrenal crisis. In our study, most hyperkalemic dogs were managed without requiring additional specific therapy (consisting of administration of either calcium gluconate and/or glucose/insulin therapy) with no difference between groups. A recent study suggested that dogs receiving HC infusion might be less likely to require emergency management of hyperkalemia, which we did not find in our cohort. ⁹

Fluid therapy represents a vital first‐line treatment for dogs presented with adrenal crisis, with mortality often ascribed to hypovolemic shock. ¹⁴ Most of the human and veterinary literature suggests normal saline as the preferred crystalloid in these patients, because of the high sodium content and absence of potassium. ⁵ , ⁸ , ⁹ However, the use of more balanced crystalloid solutions like LRS or Plasma‐Lyte 148 has been advocated because of their alkalinizing and almost negligible potassium contribution. ⁵ In our study, both solutions were used in either group in similar proportions and with no significant effect on the rate of change of either electrolytes or pH values. However, the authors recognize that the effect of fluid choice in the current study is limited by the lack of data regarding the total amount and rate of fluid administered in each individual dog.

Doses of both DEX and HC reported in our study were highly variable. The same has also been found in the previously available veterinary evidence, where the glucocorticoid dose ranges used in dogs with hypoadrenocorticism can vary between 3 and 10 times the physiological requirements. ⁵

The HC doses reported in our study group varied from 0.3 to 0.5 mg/kg/h. According to experimental studies, a dose of 0.5 to 0.625 mg/kg/h of HC provides sufficient glucocorticoid and mineralocorticoid activity to successfully correct acute adrenal hypofunction. ¹³ Although 0.3 mg/kg/h has been suggested by some authors, it could be that hormone replacement in these patients failed to reach appropriate physiological levels. ¹⁵

In the DEX group, therapeutic doses reported ranged between 0.03 mg/kg and 1 mg/kg q24h. Given that DEX has a relative glucocorticoid activity of nearly 30 times that of HC without any mineralocorticoid activity ⁹ , ¹⁶ these dose ranges would equate to 0.9 mg/kg/day (0.0375 mg/kg/h) and 30 mg/kg/day (1.25 mg/kg/h) of HC respectively. At these extremes, dogs would either have received a remarkable undersupplementation or relative excess of glucocorticoids. Even at the most commonly administered dose of 0.1 mg/kg q24h, equating to 3 mg/kg/day (0.125 mg/kg/h) of HC, it is possible that these dogs' hormone replacement never reached adequate physiological levels, possibly slowing the rate of correction of both electrolytes and acid‐base status in this study group.

Although our HC group had a slightly shorter median hospitalization time than the DEX group, the difference was not statistically significant. We do not know if this is because of the limited number of cases included in this study. This is in contrast with previous findings that showed a significantly longer hospitalization in dogs treated with HC infusion compared with a DEX or prednisolone administration. ¹⁰ However, our median hospitalization time of approximately 2 days in both groups is consistent with previous studies. ⁹ , ¹⁴

In contrast to a previous study, we did not find that dogs treated with HC infusion required more intensive monitoring, either for the overall number of checks or checks per hour. ¹⁰ This could be explained by the previous paper describing the authors' practice to monitor dogs on CRIs more intensively or a potential clinicians' bias toward the use of HC CRIs in sicker dogs, though this is considered less likely as the Acute Patient Physiological and Laboratory Evaluation fast (APPLE_fast) scores were identical in the 2 groups in that study.

The demographic of the dogs included in this study was consistent with previously published studies. The median age of our study sample was 5.95 years which is only slightly older than the previously available literature indicating a median age at diagnosis between 4 and 5 years old. ⁷ , ⁹ , ¹⁷ Poodles or poodle crosses were found to be prevalent breeds in our study cohort as identified in other studies. ⁷ , ¹⁸ , ¹⁹

This study has some noteworthy limitations, mainly because of its retrospective nature, including the overall number of cases and no standardization of care. Furthermore, because of the lack of blinding or randomization, potential clinician‐based bias toward the selection of certain cases receiving one or the other treatment cannot be excluded. For example, it is possible that more severely affected cases might have been preferentially treated with HC infusion as indicated by a lower initial serum Na and pH found in the HC group. Additionally, different blood analyzers for hematology, serum biochemistry, venous blood gas analysis, as well as disparate external reference laboratories for the ACTH stimulation tests were used at the different institutions, potentially introducing some degree of inconsistency between the absolute values obtained.

Ultimately, although HC infusion seems to be a safe treatment for dogs presented with acute Addisonian crisis and noninferior to the more traditional DEX protocol, prospective randomized control trials will be necessary to investigate this further.

This retrospective study adds to recent evidence that HC infusion is a safe and effective treatment for dogs presented with adrenal crisis. Furthermore, this protocol showed no increased risk of rapid electrolyte or acid‐base changes, no longer hospitalization times, no additional requirement for more intensive monitoring, and no increased case fatality compared to the more widespread use of DEX.

CONFLICT OF INTEREST DECLARATION

Authors declare no conflict of interest.

OFF‐LABEL ANTIMICROBIAL DECLARATION

Authors declare no off‐label use of antimicrobials.

INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) OR OTHER APPROVAL DECLARATION

Authors declare no IACUC or other approval was needed.

HUMAN ETHICS APPROVAL DECLARATION

Authors declare human ethics approval was not needed for this study.

Brunori L, Walesby OX, Lewis DH, Boag AM. A retrospective study of hydrocortisone continuous rate infusion compared with administration of dexamethasone boluses in dogs with adrenal crisis. J Vet Intern Med. 2024;38(2):951‐959. doi: 10.1111/jvim.17017